期刊
CANCER LETTERS
卷 230, 期 2, 页码 228-238出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2004.12.043
关键词
Ginsenoside-Rh2; protein kinase C delta; caspase-3; SK-HEP-1; apoptosis; cytochrome c
类别
Ginsenoside-Rh2 (G-Rh2) has been shown to induce apoptosis in a variety of cell types. In this study, we show that G-Rh2-induced apoptosis is accompanied by the mitochondrial release of cytochrome c and activation of caspase-3 in the human hepatoma cell line, SK-HEP-1. Furthermore, protein kinase C delta (PKC delta) activity was markedly up-regulated in a lipid activator-independent manner with kinetics similar to those of PKC delta and PARP cleavages during the apoptotic progression. Pre-treatment of cells with the caspase-3 specific inhibitor (z-DEVD-fmk) effectively prevented the G-Rh2-induced proteolytic activation of PKC delta. Moreover, rottlerin, a specific PKC delta inhibitor blocked G-Rh2-induced proapoptotic effects on the cells including the release of cytochrome c, activation of caspase-3 activity, and proteolytic cleavage and activation of PKC delta. These results suggest that G-Rh2-induced apoptosis is functionally linked to mitochondrial dysfunction and caspase-3 activity is regulated by positive feedback with PKC delta via the mitochondrial pathway. (c) 2005 Elsevier Ireland Ltd. All rights reserved.
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